CD80 Costimulation Is Essential for the Induction of Airway Eosinophilia

CD80 and CD86 (B7-1 and B7-2) are the ligands on antigen-presenting cells (APCs) which bind CD28 and deliver the costimulatory signals necessary for T cell activation. The reasons for the existence of two CD28 binding molecules are not well understood. We created a mutant version of CTLA4-Ig that could selectively bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact. CD80 blockade prevented antigen-induced accumulation of eosinophils and lymphocytes in the lung of immunized mice, but did not block antigen induced systemic blood eosinophilia or IgE antibody production. No preferential expression of CD80 could be demonstrated on a population of lung APC consisting mainly of macrophages. These results indicate that CD80 costimulation is not necessary for the induction of Th2 immune responses but rather for the maintenance or amplification of lung inflammatory responses.

[1]  P. Linsley,et al.  Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. , 1992, Science.

[2]  J. Bluestone,et al.  Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. , 1995, Immunity.

[3]  J. Allison,et al.  Identification and distribution of the costimulatory receptor CD28 in the mouse. , 1992, Journal of immunology.

[4]  P. Linsley,et al.  Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. , 1994, Immunity.

[5]  R. Karr,et al.  Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. , 1995, Journal of immunology.

[6]  N. Copeland,et al.  Mouse Eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. , 1996, Immunity.

[7]  Laurie H Glimcher,et al.  B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy , 1995, Cell.

[8]  B. Hausmann,et al.  Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo , 1994, The Journal of experimental medicine.

[9]  P. Linsley,et al.  CTLA-4 is a second receptor for the B cell activation antigen B7 , 1991, The Journal of experimental medicine.

[10]  H Nakajima,et al.  Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue , 1994, The Journal of experimental medicine.

[11]  P. Linsley,et al.  Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. , 1993, Science.

[12]  P. Linsley,et al.  Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. , 1992, Science.

[13]  K. Takatsu,et al.  CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. , 1992, The American review of respiratory disease.

[14]  B. Dewald,et al.  Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. , 1994, Advances in immunology.

[15]  L. Lanier,et al.  B70 antigen is a second ligand for CTLA-4 and CD28 , 1993, Nature.

[16]  P. Foster,et al.  Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model , 1996, The Journal of experimental medicine.

[17]  P. Linsley,et al.  CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. , 1995, Journal of immunology.

[18]  P. Linsley,et al.  Treatment of murine lupus with CTLA4Ig. , 1994, Science.

[19]  Martin Bachmann,et al.  Disruption of the murine IL-4 gene blocks Th2 cytokine responses , 1993, Nature.

[20]  P. Linsley,et al.  T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Bluestone,et al.  Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse , 1995, The Journal of experimental medicine.

[22]  M. Baggiolini,et al.  CC chemokines in allergic inflammation. , 1994, Immunology today.

[23]  P. Linsley,et al.  Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes , 1992, The Journal of experimental medicine.

[24]  K. Rajewsky,et al.  Generation and analysis of interleukin-4 deficient mice. , 1991, Science.

[25]  G. Freeman,et al.  Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice. , 1993, Science.

[26]  M. Azuma,et al.  Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule , 1995, European journal of immunology.

[27]  J. Gribben,et al.  Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. , 1993, Science.

[28]  J. Bluestone,et al.  Expression and functional significance of an additional ligand for CTLA-4. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Gribben,et al.  B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. , 1995, Immunity.

[30]  Franca Ronchese,et al.  Blockade of CD28/B7 co‐stimulation by mCTLA4‐Hγ1 inhibits antigen‐induced lung eosinophilia but not Th2 cell development or recruitment in the lung , 1997, European journal of immunology.

[31]  P. Linsley,et al.  Complementarity determining region 1 (CDR1)- and CDR3-analogous regions in CTLA-4 and CD28 determine the binding to B7-1 , 1994, The Journal of experimental medicine.